Risk Of Parkinson's Disease Research Articles

The Black and African American Connections to Parkinson’s Disease (BLAAC PD) study protocol

Determining the genetic contributions to Parkinson’s disease (PD) across diverse ancestries is a high priority as this work can guide therapeutic development in a global setting. The genetics of PD spans the etiological risk spectrum, from rare, highly deleterious variants linked to monogenic forms with Mendelian patterns of inheritance, to common variation involved in sporadic disease. A major limitation in PD genomics research is lack of racial and ethnic diversity. Enrollment disparities have detrimental consequences on the generalizability of results and exacerbate existing inequities in care. The Black and African American Connections to Parkinson’s Disease (BLAAC PD) study is part of the Global Parkinson’s Genetics Program, supported by the Aligning Science Across Parkinson’s initiative. The goal of the study is to investigate the genetic architecture underlying PD risk and progression in the Black and/or African American populations. This cross-sectional multicenter study in the United States has a recruitment target of up to 2,000 individuals with PD and up to 2,000 controls, all of Black and/or African American ancestry. The study design incorporates several strategies to reduce barriers to research participation. The multifaceted recruitment strategy aims to involve individuals with and without PD in various settings, emphasizing community outreach and engagement. The BLAAC PD study is an important first step toward informing understanding of the genetics of PD in a more diverse population.

The role of genetically predicted serum iron levels on neurodegenerative and cardiovascular traits.

Iron is an essential mineral that supports numerous biological functions. Studies have reported associations between iron dysregulation and certain cardiovascular and neurodegenerative diseases, but the direction of influence is not clear. Our goal was to use computational approaches to better understand the role of genetically predicted iron levels on disease risk. We meta-analyzed genome-wide association study summary statistics for serum iron levels from two cohorts and two previous meta-analyses. We then obtained summary statistics from 11 neurodegenerative, cerebrovascular, cardiovascular or lipid traits to assess global and regional genetic correlation between iron levels and these traits. We used two-sample Mendelian randomization (MR) to estimate causal effects. Sex-stratified analyses were also carried out to identify effects potentially differing by sex. Overall, we identified three significant global correlations between iron levels and (i) coronary heart disease, (ii) triglycerides, and (iii) high-density lipoprotein (HDL) cholesterol levels. A total of 194 genomic regions had significant (after correction for multiple testing) local correlations between iron levels and the 11 tested traits. MR analysis revealed two potential causal relationships, between genetically predicted iron levels and (i) total cholesterol or (ii) non-HDL cholesterol. Sex-stratified analyses suggested a potential protective effect of iron levels on Parkinson's disease risk in females, but not in males. Our results will contribute to a better understanding of the genetic basis underlying iron in cardiovascular and neurological health in aging, and to the eventual identification of new preventive interventions or therapeutic avenues for diseases which affect women and men worldwide.

Prospective Study of Lung Function with Prodromal, Clinical Parkinson's Disease, and Mortality.

The association of lung function with the risk of developing prodromal and clinical-diagnosed Parkinson's disease (PD) and with the risk of mortality among individuals with PD remains unknown. To prospectively examine the associations of lung function with the risk of prodromal, clinical-diagnosed PD, and PD-related mortality in participants of the UK Biobank. Included were 452,518 participants free of PD at baseline. Baseline lung function, including forced expiratory volume in 1-s (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), and FEV1/FVC ratio, was assessed. Eight prodromal features were measured using self-reported diagnoses, hospital admission, and primary care data. Incident PD cases were identified using linkages with hospital admission, death register, and self-report. Vital status and date of death were provided by the UK National Health Service (NHS) and the NHS Central Register. We used Cox proportional hazard models to evaluate these associations. Poor lung function was associated with higher risk of PD in a dose-response relationship: the adjusted hazard ratio comparing the lowest vs. the highest lung function quintile was 1.18 (95% CI, 1.02- 1.37) for FEV1, 1.14 (95% CI, 0.99- 1.29) for FVC, and 1.23 (95% CI, 1.08- 1.41) for PEF (p-trend <0.05 for all). Similar results were obtained for risk of prodromal PD and mortality among individuals with PD. The current study showed that individuals with poor lung function had a high future risk of prodromal and clinical PD and a higher rate of PD-related mortality.

Infections in the Etiology of Parkinson's Disease and Synucleinopathies: A Renewed Perspective, Mechanistic Insights, and Therapeutic Implications.

Increasing evidence suggests a potential role for infectious pathogens in the etiology of synucleinopathies, a group of age-related neurodegenerative disorders including Parkinson's disease (PD), multiple system atrophy and dementia with Lewy bodies. In this review, we discuss the link between infections and synucleinopathies from a historical perspective, present emerging evidence that supports this link, and address current research challenges with a focus on neuroinflammation. Infectious pathogens can elicit a neuroinflammatory response and modulate genetic risk in PD and related synucleinopathies. The mechanisms of how infections might be linked with synucleinopathies as well as the overlap between the immune cellular pathways affected by virulent pathogens and disease-related genetic risk factors are discussed. Here, an important role for α-synuclein in the immune response against infections is emerging. Critical methodological and knowledge gaps are addressed, and we provide new future perspectives on how to address these gaps. Understanding how infections and neuroinflammation influence synucleinopathies will be essential for the development of early diagnostic tools and novel therapies.

6-O-alkyl 4-methylumbelliferyl-β-D-glucosides as selective substrates for GBA1 in the discovery of glycosylated sterols

Gaucher disease (GD) is a lysosomal storage disorder (LSD) resulting from inherited glucocerebrosidase (GBA1) deficiency. GD diagnosis relies on GBA1 activity assays, typically employing 4-methylumbelliferyl-β-D-glucopyranoside (4MU-β-Glc) as fluorogenic substrate. However, these assays suffer from background 4MU release by the non-lysosomal GBA2 and cytosolic GBA3 enzymes. Here we developed GBA1-selective fluorogenic substrates by synthesizing a series of 6-O-acyl-4MU-β-Glc substrates with diverse fatty acid tails. Because of the chemical and enzymatic instability of the ester bonds, analogs of 6-O-palmitoyl-4MU-β-Glc (3) with different chemical linkages were synthesized. 6-O-alkyl-4MU-β-Glc 9, featuring an ether linkage, emerged as the most optimal GBA1 substrate, exhibiting both a low Km and compared to substrate 3 a high Vmax. Importantly, substrate 9 is not hydrolyzed by GBA2 and GBA3 and therefore acts as a superior substrate for GD diagnosis. Plants contain glycosyl phytosterols (campesterol, β-sitosterol, and sigmasterol) that may also be acylated at C-6. LC-MS/MS analysis revealed that 6-O-acylated and regular glycosylcholesterol (HexChol) tend to be increased in spleens of patients with GD. Moreover, significant increases in 6-O-acyl-glycosyl-phytosterols were detected in GD spleens. Our findings suggest uptake of (6-O-acyl)-glycosyl-phytosterols from plant food and subsequent lysosomal processing by GBA1, and comprise the first example of accumulation of an exogenous class of glycolipids in GD. Excessive exposure of rodents to glycosylated phytosterols has been reported to induce manifestations of Parkinson’s disease (PD). Further investigation is warranted to determine whether (6-O-acyl)-glycosyl-phytosterols could contribute to the enigmatic link between inherited defects in GBA1 and the risk for PD.

Investigating the Genetic Association of 40 Biochemical Indicators with Parkinson's Disease.

The mechanisms of Parkinson's disease (PD) are not fully understood, which hinders the development of effective therapies. Research indicates that lower levels of biochemical indicators like bilirubin, vitamin D, and cholesterol may elevate the risk of PD. However, clinical studies on abnormal levels of biochemical indicators in PD patients' circulation are inconsistent, leading to ongoing debate about their association with PD. Here, we investigate the genetic correlation between 40 biochemical indicators and PD using a bidirectional two-sample Mendelian randomization (MR) approach to uncover potential causal relationships. Data from genome-wide association studies (GWAS) were utilized, with genetic variations from specific lineages serving as instrumental variables (IVs). The methodology followed the STROBE-MR checklist and adhered to the three principal assumptions of MR. Statistical analyses employed methods including inverse variance weighting (IVW), MR-Egger, weighted median, and weighted mode. Biochemical indicators including albumin, C-reactive protein (CRP), and sex hormone-binding globulin (SHBG) showed significant associations with PD risk. Elevated levels of albumin (OR = 1.246, 95% CI 1.006-1.542, P = 0.043) and SHBG (OR = 1.239, 95% CI 1.065-1.439, P = 0.005) were linked to higher PD risk. Conversely, increased CRP levels (OR = 0.663, 95% CI 0.517-0.851; P = 0.001) could potentially lower PD risk. The robustness of the results was confirmed through various MR analysis techniques, including assessments of directional pleiotropy and heterogeneity using MR-Egger intercept and MR-PRESSO methods. This study systematically reveals, for the first time at the genetic level, the relationship between 40 biochemical indicators and PD risk. Our research verifies the role of inflammation in PD and provides new genetic evidence, further advancing the understanding of PD pathogenesis. The study shows a positive correlation between albumin and SHBG with PD risk and a negative correlation between CRP and PD risk. This study identifies for the first time that SHBG may be involved in the onset of PD and potentially worsen disease progression.

Risk of Parkinson’s disease in spinal cord injury: a nationwide cohort study in South Korea

Despite the association between spinal cord injury (SCI) and various neurological diseases, the risk of Parkinson’s disease (PD) in SCI is not elucidated yet. Especially, the role of SCI severity and injury level in the risk of PD development is not investigated. Based on the nation-wide cohort data the Korean National Health Insurance Service between 2010 and 2018, we investigated the incidence of PD in 7,182 patients with SCI compared with 24,844 age- and sex-matched controls. Adjusted hazard ratio and 95% confidence interval (CI) were calculated using Cox proportional hazards regression. We compared the risk of PD based on the degree of disability (without disability, mild, severe) and SCI level (cervical, thoracic, and lumbar). During the mean follow-up duration of 4.31 years, patients with SCI had a higher risk of PD compared with matched controls. The PD risk was greater among patients with SCI with disability than in those without disability, especially those with mild disability. Additionally, cervical-level injury was associated with the highest risk in patients with SCI without disability, while thoracic-level injury was associated with the highest risk in those with disability. Our study found patients with SCI have increased risk of PD, particularly those with disability and thoracic-level injuries.

Physical activity and risk of Parkinson's disease: an updated systematic review and meta-analysis.

Although recent meta-analyses have shown that the association between physical activity (PA) and the risk of developing Parkinson's disease (PD) is influenced by gender differences, a growing number of studies are revealing the general applicability of this association across genders. This study aimed to reassess the association and dose-response relationship between PA and PD risk in populations. A systematic search of PubMed, Embase, Cochrane Library, and Web of Science databases was conducted in this study from inception to February 1, 2024, without language restrictions. Stratified analyses were conducted to explore the association between PA and PD risk, combining multivariate-adjusted effect estimates via random-effects models, and to validate the dose-response relationship between the two. This study included 21 observational studies, comprising 13 cohort studies and 8 case-control studies. The pooled analysis revealed that PA significantly reduced the risk of developing PD [relative risk (RR) = 0.77, 95% CI 0.70-0.85]. In addition, the dose-response analysis revealed both linear and nonlinear associations, with linear results indicating a 9% reduction in PD risk for every 10 MET-h/wk increase in PA. The study also demonstrated that the protective effect of PA against PD was significant for both sexes. Moreover, no statistically significant effects of PA on preventing PD were observed in individuals with a BMI > 26 (RR = 0.35, 95% CI 0.12-1.02) or in Asian populations (RR = 0.78, 95% CI 0.60-1.01); however, the trends suggest potential protective effects, warranting further investigation. Sensitivity analyses confirmed the robustness of these findings. This meta-analysis produced substantial evidence to reaffirm the protective effect of high PA on PD across various population groups and the inverse dose-response relationship with PD risk, and to validate the protective effect of PA among different demographic groups.

Prospective study of bipolar disorder and neurodegenerative diseases

Bipolar disorder (BD) is linked to an increased risk of neurodegenerative diseases such as dementia and Parkinson disease (PD), yet several uncertainties still remain and the extent to which the associations could be explained by BD-related medications (antipsychotics, lithium, and antiepileptics) was unknown. This study included 501,233 UK Biobank participants (mean [standard deviation] age, 56.5 [8.10] years; 54.4% women), free of dementia and PD at baseline. After a median 13.8 year follow-up, 9422 cases of dementia and 3457 PD cases were identified. Participants with BD had a significantly higher risk of dementia (adjusted hazard ratio [HR] 2.52, 95% CI 2.00–3.19) and PD (adjusted HR 2.88, 95% CI 2.03-4.08). Findings suggest that up to two-thirds of the association of neurodegenerative diseases with BD may be mediated by BD-related medications. Further research is needed to confirm these findings and explore the underlying mechanisms.

LRRK2 regulates production of reactive oxygen species in cell and animal models of Parkinson's disease.

Oxidative stress has long been implicated in Parkinson's disease (PD) pathogenesis, although the sources and regulation of reactive oxygen species (ROS) production are poorly defined. Pathogenic mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) are associated with increased kinase activity and a greater risk of PD. The substrates and downstream consequences of elevated LRRK2 kinase activity are still being elucidated, but overexpression of mutant LRRK2 has been associated with oxidative stress, and antioxidants reportedly mitigate LRRK2 toxicity. Here, using CRISPR-Cas9 gene-edited HEK293 cells, RAW264.7 macrophages, rat primary ventral midbrain cultures, and PD patient-derived lymphoblastoid cells, we found that elevated LRRK2 kinase activity was associated with increased ROS production and lipid peroxidation and that this was blocked by inhibitors of either LRRK2 kinase or NADPH oxidase 2 (NOX2). Oxidative stress induced by the pesticide rotenone was ameliorated by LRRK2 kinase inhibition and was absent in cells devoid of LRRK2. In a rat model of PD induced by rotenone, a LRRK2 kinase inhibitor prevented the lipid peroxidation and NOX2 activation normally seen in nigral dopaminergic neurons in this model. Mechanistically, LRRK2 kinase activity was shown to regulate phosphorylation of serine-345 in the p47phox subunit of NOX2. This, in turn, led to translocation of p47phox from the cytosol to the membrane-associated gp91phox (NOX2) subunit, activation of the NOX2 enzyme complex, and production of ROS. Thus, LRRK2 kinase activity may drive cellular ROS production in PD through the regulation of NOX2 activity.

Investigation of the causal relationship between cholelithiasis and Parkinson's disease: A bidirectional Mendelian randomization study.

Parkinson's disease (PD) and cholelithiasis are a huge public health burden. Although observational studies have suggested a potential link between PD and cholelithiasis, the causal relationship between the two remains uncertain. To address this gap, we performed a two-sample bidirectional Mendelian randomization analysis using genetic tools. Genome-wide association study summary statistics for all traits were obtained from publicly available databases. We used strict control steps in instrumental variable selection to screen for single nucleotide polymorphisms (SNPs) from summary-level genome-wide association studies. In addition, all F-statistics were >10, indicating no weak instrumental bias. The inverse variance weighting (IVW) method was the primary method used to assess causal associations. Four other MR methods (MR-Egger, Weighted Median, Simple mode, and Weighted mode) were also used to complement IVW. Various sensitivity tests were also performed to assess reliability: (1) Cochrane's Q test for assessing heterogeneity, (2) MR-Egger intercept test and MR-PRESSO global test for assessing horizontal multiplicity, and (3) leave-one-out sensitivity test for determining stability. We selected a total of 30 SNPs as instrumental variables. It was demonstrated that cholelithiasis had a causal effect on the risk of PD (OR = 1.146, 95% CI: 1.062-1.236, p < 0.001) in IVW method. The results of our analysis revealed an increased risk effect of cholelithiasis against PD, which may give light on new approaches to PD prevention and therapy.

Association Between Serum Galectin-3 and Parkinson's Disease: A Two-Sample Mendelian Randomization Study.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder with poor prognosis. Observational studies have demonstrated a significant correlation between serum galectin-3 and PD, suggesting a potential role of galectin-3 as a biomarker for PD. However, it is still unclear whether galectin-3 contributes to the risk of the disease. A two-sample Mendelian randomization (MR) approach was used in this study. Genetic instruments for serum galectin-3 level were selected from a genome-wide association study (GWAS), including 30,931 European individuals. Summary-level statistics for PD were derived from another published GWAS, including 33,674 cases and 449,056 controls. Primary analysis was conducted using the inverse-variance weighting (IVW) method. Weighted median, MR-Egger, simple mode, weighted mode, and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods were used as complementary analyses. To detect heterogeneity, Cochran's Q statistic and leave-one-out analysis were used. For testing potential horizontal pleiotropy, the MR-Egger intercept test and MR-PRESSO global test were conducted. MR analysis using IVW model (OR 1.112, 95% CI 1.025-1.206, p = 0.010), weighted median (OR 1.135, 95% CI 1.037-1.242, p = 0.006), weighted mode (OR 1.142, 95% CI 1.038-1.257, p = 0.030), and MR-PRESSO (OR 1.112, 95% CI 1.046-1.182, p = 0.012) presented a consistent result, indicating that increased serum galectin-3 was associated with a higher risk of PD. No heterogeneity or horizontal pleiotropy was detected in the analyses. The study shows a suggestive association between galectin-3 and PD. Increasing serum galectin-3 was associated with an increase in PD risk. Galectin-3 may play an important role in the causal pathway to PD.

Genetic Analysis of Neurite Outgrowth Inhibitor-Associated Genes in Parkinson's Disease: A Cross-Sectional Cohort Study.

Parkinson's disease (PD) is a neurodegenerative disease caused by a combination of aging, environmental, and genetic factors. Previous research has implicated both causative and susceptibility genes in PD development. Nogo-A, a neurite outgrowth inhibitor, has been shown to impact axon growth through ligand-receptor interactions negatively, thereby involved in the deterioration of dopaminergic neurons. However, rare genetic studies have identified the relationship between neurite outgrowth inhibitor (Nogo)-associated genes and PD from a signaling pathway perspective. We enrolled 3959 PD patients and 2931 healthy controls, categorized into two cohorts based on their family history and age at onset: sporadic early Parkinson's disease & familial Parkinson's disease (sEOPD & FPD) cohort and sporadic late Parkinson's disease (sLOPD) cohort. We selected 17 Nogo-associated genes and stratified them into three groups via their function, respectively, ligand, receptors, and signaling pathway groups. Additionally, we conducted the burden analysis in rare variants, the logistic regression analysis in common variants, and the genotype-phenotype association analysis. Last, bioinformatics analysis and functional experiments were conducted to identify the role of the MTOR gene in PD. Our findings demonstrated that the missense variants in the MTOR gene might increase PD risk, while the deleterious variants in the receptor subtype of Nogo-associated genes might mitigate PD risk. However, common variants of Nogo-associated genes showed no association with PD development in two cohorts. Furthermore, genotype-phenotype association analysis suggested that PD patients with MTOR gene variants exhibited relatively milder motor symptoms but were more susceptible developing dyskinesia. Additionally, bioinformatics analysis results showed MTOR gene was significantly decreased in PD, indicating a potential negative role of the mTOR in PD pathogenesis. Experimental data further demonstrated that MHY1485, a mTOR agonist, could rescue MPP+-induced axon inhibition, further implicating the involvement of mTOR protein in PD by regulating cell growth and axon growth. Our preliminary investigation highlights the association of Nogo-associated genes with PD onset in the Chinese mainland population and hints at the potential role of the MTOR gene in PD. Further research is warranted to elucidate the mechanistic pathways underlying these associations and their therapeutic implications.

LRRK2; Communicative Role in the Treatment of Parkinson's Disease and Ulcerative Colitis Overlapping.

Involvement of gastrointestinal inflammation in Parkinson's disease (PD) pathogenesis and movement have progressively emerged. Inflammation is involved in the etiology of both PD and inflammatory bowel disease (IBD). Transformations in leucine-rich recurrent kinase 2 (LRRK2) are among the best hereditary supporters of IBD and PD. Elevated levels of LRRK2 have been reported in stimulated colonic tissue from IBD patients and peripheral invulnerable cells from irregular PD patients; thus, it is thought that LRRK2 directs inflammatory cycles. Since its revelation, LRRK2 has been seriously linked in neurons, albeit various lines of proof affirmed that LRRK2 is profoundly communicated in invulnerable cells. Subsequently, LRRK2 might sit at a junction by which stomach inflammation and higher LRRK2 levels in IBD might be a biomarker of expanded risk for inconsistent PD or potentially may address a manageable helpful objective in incendiary sicknesses that increment the risk of PD. Here, we discuss how PD and IBD share covering aggregates, especially regarding LRRK2 and present inhibitors, which could be a helpful objective in ongoing treatments. English data were obtained from Google Scholar, PubMed, Scopus, and Cochrane library studies published between 1990-December 2022. Inhibitors of the LRRK2 pathway can be considered as the novel treatment approaches for IBD and PD treatment. Common mediators and pathways are involved in the pathophysiology of IBD and PD, which are majorly correlated with inflammatory situations. Such diseases could be used for further clinical investigations.

A cross sectional study to assess the knowledge, attitude and risk of Parkinson Disease among older adults

A cross sectional study to assess the knowledge, attitude and risk of Parkinson Disease among older adults

Exploring the Nicotine-Parkinson's disease link – Insights from the UK Biobank

IntroductionEvidence suggests an inverse correlation between smoking and Parkinson's disease (PD), yet the mechanisms remain unclear. This study examines the changing risk relationship between smoking and PD diagnosis using alcohol consumption, another reward-driven behavior, as a comparative measure. MethodsA nested case-control study was conducted using the UK Biobank (UKBB) database. Participants in the prediagnostic phase of PD were identified, and self-reported data on tobacco and alcohol use were analyzed employing conditional binary logistic regression. Polynomial and piece-wise regression models were employed to discern shifting associations with PD over time. ResultsOf 502,304 participants (63 ± 5.3 years, 63 % male), 3049 prediagnostic PD cases were identified. Non-smokers had a heightened PD risk, and this association strengthened closer to diagnosis. The odds ratio (OR [95 % CI]) associated with PD in non-smokers was 2.02 [1.07–3.81] 1–4 years before diagnosis, compared to 1.36 [1.02–1.83] at >10-year intervals (linear trend, p = 0.012). The time trajectory of ORs was best depicted by a quadratic function, identifying a shift in risk 7.5 years before diagnosis documentation. Similar patterns emerged among alcohol non-consumers, with an 8.5-year interval inflection point. ConclusionThis study identified two disparate risk trajectories among non-smokers: an initial low-amplitude increased risk at prolonged prediagnostic intervals possibly related to genetic/personality factors, followed by a sharp escalation in risk association commencing 7–8 years before diagnosis, possibly propelled by reverse causality. Similar trends in alcohol consumption reinforce these conclusions. These findings could suggest that smoking cessation may serve as an early indicator of PD.

Migraine and Risk of Parkinson Disease in Women: A Cohort Study.

Migraine and Parkinson disease (PD) are common neurologic disorders, which are hypothesized to share some pathophysiologic mechanisms. However, data on the association between migraine and risk of developing PD are sparse. We estimate the effect of migraine, migraine subtypes, and migraine episode frequency on the risk of developing PD in middle-aged and older women. We used data from the Women's Health Study, a United States-based cohort of women in health professions aged 45 years and older at baseline (1992-1995). Only women with complete self-reported information on migraine and headache and no history of PD were included. Participants were followed up for self-reported physician-diagnosed PD through December 31, 2021. We used multivariable Cox proportional hazards models to estimate hazard ratios (HRs) and corresponding 95% CIs of the association between migraine, migraine subtypes, and migraine episode frequency and the risk of developing PD. A total of 39,312 women were included in the analyses. Among those, 7,321 women (18.6%) reported any migraine at baseline, of whom 2,153 (5.5%) reported a history of migraine, 2,057 (5.2%) reported migraine with aura, and 3,111 (7.9%) reported migraine without aura. During a mean follow-up of 22.0 years, 685 PD cases were reported. Of those, 128 (18.7%) were reported by women who also reported any migraine and 557 (81.3%) by women without any migraine. After adjusting for confounding, the HR for the association of any migraine on the risk of PD was 1.07 (0.88-1.29). Compared with women without migraine, the HRs (95% CI) for PD were 0.87 (0.59-1.27) for migraine with aura, 1.21 (0.93-1.58) for migraine without aura, and 1.05 (0.76-1.45) for history of migraine. Compared with those with a migraine frequency of less than monthly, the HRs were 1.09 (0.64-1.87) for a monthly frequency and 1.10 (0.44-2.75) for a weekly or greater frequency. In this large cohort of women, the risk of developing PD was not elevated among those experiencing migraine, irrespective of migraine subtypes or the frequency of migraine. The generalizability of our findings to other populations, such as men, should be further investigated. ClinicalTrials.gov Identifier: NCT00000479.

Anemia, blood cell indices, genetic correlations, and brain structures: A comprehensive analysis of roles in Parkinson's disease risk

IntroductionAnemia may contribute significantly to the onset of Parkinson's disease (PD). Current research on the association between anemia and PD risk is inconclusive, and the relationships between anemia-related blood cell indices and PD incidence require further clarification. This study aims to investigate the relationships between anemia, blood cell indicators, and PD risk using a thorough prospective cohort study. MethodsWe used data from the UK Biobank, a prospective cohort study of 502,649 participants, and ultimately, 365,982 participants were included in the analysis. Cox proportional hazards models were utilized to adjust for confounding factors, aiming to thoroughly explore the associations between anemia and blood cell indices with the risk of incident PD. The interaction between anemia and Polygenic Risk Score (PRS) for PD was also examined. Linear regression and mediation analyses assessed potential mechanisms driven by brain structures, including grey matter volume. ResultsDuring a median follow-up of 14.24 years, 2513 participants were diagnosed with PD. Anemia considerably increased PD risk (hazard ratio [HR] 1.98, 95 % confidence interval [CI]: 1.81–2.18, P < 0.001) after adjustments. Those with high PRS for anemia had an 83 % higher PD incidence compared to low PRS participants. Sensitivity analyses confirmed result robustness. Linear regression showed that anemia correlated with grey matter volumes and most white matter tracts. Furthermore, mediation analyses identified that the volume of grey matter in Thalamus mediates the relationship between anemia and PD risk. ConclusionIn summary, we consider there to be a substantial correlation between anemia and increased PD risk.

Neuroanatomical and prognostic associations of depression in Parkinson’s disease

BackgroundDepression is reported as a risk factor, prodromal feature and late consequence of Parkinson’s disease (PD). We aimed to evaluate the timing, neuroanatomy and prognostic implications of depression in PD.MethodsWe...

Role of Glutathione in Parkinson's Disease Pathophysiology and Therapeutic Potential of Polyphenols.

Oxidative stress is recognized to have a central role in the initiation and progression of Parkinson's disease (PD). Within the brain, neurons are particularly sensitive to oxidation due in part to their weak intrinsic antioxidant defense. Theoretically, neurons mostly depend on neighboring astrocytes to provide antioxidant protection by supplying cysteine-containing products for glutathione (GSH) synthesis. Astrocytes and neurons possess several amino acid transport systems for GSH and its precursors. Indeed, GSH is the most abundant intrinsic antioxidant in the central nervous system. The GSH depletion and/or alterations in its metabolism in the brain contribute to the pathogenesis of PD. Noteworthy, polyphenols possess potent antioxidant activity and can augment the GSH redox system. Numerous in vitro and in vivo studies have indicated that polyphenols exhibit potent neuroprotective effects in PD. Epidemiological studies have found an association between the consumption of dietary polyphenols and a lower PD risk. In this review, we summarize current knowledge on the biosynthesis and metabolism of GSH in the brain, with an emphasis on their contribution and therapeutic potential in PD. In particular, we focus on polyphenols that can increase brain GSH levels against PD. Furthermore, some current challenges and future perspectives for polyphenol-based therapies are also discussed.